Two images compare brain scans from an older individual who had Alzheimer’s (left) with an older cognitively healthy individual (right).

In most of the human body, the lymphatic system clears away waste and toxins. The brain, however, has no lymphatic vessels. Its waste, including plaques associated with Alzheimer’s disease, is cleaned instead by cerebrospinal fluid recirculating through brain tissue. Over the course of five years, research in the lab of Jeffrey Iliff, Ph.D., has defined this brain-wide paravascular pathway, called the glymphatic system.

Iliff’s team has found that this recirculation is modulated by sleep and also that, as the brain ages, this waste-clearing process is impaired. Their work continues to investigate what causes the glymphatic system to slow. In research findings published November 28 in the journal JAMA Neurology, Iliff demonstrates the possible role of aquaporin-4, a membrane protein in the brain and key component of the glymphatic system.

The study examined 79 brains donated through the Oregon Brain Bank, a part of the OHSU Layton Aging and Alzheimer’s Disease Center. Researchers found that in the brains of younger people and older people without Alzheimer’s, the aquaporin-4 protein was well organized, lining the blood vessels of the brain. However, within the brains of people with Alzheimer’s, the aquaporin-4 protein appeared disorganized, which may reflect an inability of these brains to efficiently clear away wastes like amyloid beta.

The study suggests that future research focusing on aquaporin-4 might find it to be a useful target for potentially preventing and treating Alzheimer’s disease.

This work was supported by funding from the American Heart Association, grant 12SDG11820014, the Oregon Partnership for Alzheimer’s Research, grants from the Research and Development Office of the Department of Veterans Affairs and the National Institutes of Health (NS089709), including Alzheimer’s Disease Center grant AG08017 from the National Institute on Aging that supported the longitudinal follow-up and subsequent brain autopsies providing the human brain samples used in this study.

Vinay Prasad, M.D., M.P.H., is a hematologist-oncologist and assistant professor in the OHSU School of Medicine. He is nationally known for his research on health policy, evidence-based medicine, bias, and medical reversal. Clinically, Dr. Prasad specializes in the care of lymphoma patients. He holds appointments in the Department of Public Health and Preventive Medicine and the Center for Health Care Ethics, where he is a Senior Scholar. We sat down with Dr. Prasad to talk about the formation of his career, his current projects, and where he sees his work going.

What’s your background?

I’m a Midwesterner from the Chicago area, and I didn’t stray far from home when I started college — I went to Michigan State University and then the University of Chicago. At MSU, I studied philosophy, writing, and science from several terrific professors, who pushed us really hard to think about our assumptions, and question them.

That was a good foundation for my experience at the University of Chicago as a medical student, which was a really special place for people who were thinking critically about medicine. I had a chance to work with physicians who cared about medical ethics, as well as those who cared about medical evidence, and all of them were superb. Finally, I completed my training at Northwestern University — where I had still more excellent role models in evidence-based medicine, and my hematology-oncology training at the National Institutes of Health, which, for me, was the ideal place to train.

When we think of medicine, we think of science, of proof. But it wasn’t until the 70s, 80s, and 90s, that we really developed a field of medicine that prioritized evidence. Before, this time though evidence was used here and there, the bulk of what you learned as a doctor was based on some very senior person telling you that’s how things were done — “This is how you recognize disease and this is what you do about it.” It comes as a shock to people outside of medicine that all medicine wasn’t always based on evidence, and, to some degree, still is not.

What knowledge do you want to see medical students graduate with?

First, you want doctors to be conscious of bedside manner. In 2016, it is of paramount importance to be good at that, and I think our training is getting much better at teaching the right skills.

Second, medical students definitely should graduate knowing how to think critically, evaluate a paper, and how to interpret statistics. The more you practice medicine, it becomes less about memorization and more about critical thinking. I also think that critical thinking is not synonymous with forced research projects. I think maybe we should move away from thinking medical students should graduate with a few research abstracts on their CV, which often rely on very unreliable methods—because that is what can get done in the time allotted. Instead, I think we have to teach the appraisal of medical evidence much more formally—much greater emphasis on study design, reliability, and how to make inferences from data. We have to teach students that medicine in the 21st century is a field where you will always be learning.

The prerequisites for medical school are tangential to medical school — calculus, physics, and organic chemistry — not to say there are no doctors that use those, but most don’t. People say those prerequisites teach you critical thinking, that they teach you memorization. But there are better ways to teach memorization and critical thinking. Philosophy is arguably something that trains you to think very critically; logic trains you to think critically; statistics too. I would consider those things. But again I would experiment, rather than mandate.

It was really in the last year of medical school and the first year of my residency that I got interested in research. I always thought I’d simply go into private practice —then, on a whim almost, I submitted a paper I had worked on — a paper that some senior person deemed “not scholarship”— to a journal. It ended up being published in the Hastings Center report. It’s fair to say that the kind of research I do — not many make a career of it. So it took me a while to realize that you can have any kind of career you want. You just keep doing it and eventually someone calls it a career.

What research are you conducting now?

Well, we have a lot of projects underway. A lot of what we’re doing is at the intersection of policy and funding and we’re doing a lot of work on is how we should pay for medical practices. If you’re in oncology, the cost of drugs is something that you cannot avoid. And we’re doing a little bit of work on in conflict of interest, prioritizing randomized-controlled trials, and some about research funding.

My goal is to try to do work that’s impactful. I aspire to do work that is read and hopefully leads people to change. For that reason I abandon a lot of projects at the outset — projects that I don’t think will be impactful, or will be published in one of the fifty thousand journals that frankly, no one reads. So, I think a lot about what I want the work to be.

Studying FDA drug approval is a big thing. Because, while there are a few drugs that are wonderful, a lot of the drugs the FDA approves are very marginal. So we’re doing a lot of work to ask should those drugs be approved, how should they be studied if they are approved, and under what circumstances should they be pulled off the market.

We have a new paper in JAMA Oncology where we start with what I think is an uncontroversial premise — that the purpose of the FDA is to approve drugs that improve survival or quality of life for people in America. That’s their purpose.

A simple fact is that the majority of drugs approved in cancer over the last 10 years are marginal. The median improvement in survival is about two months. And the clinical trials they’re conducted in are unrepresentative — they study younger and healthier patients. And, finally, when you look at how unrepresentative marginal drugs do in the real world, the answer is that they don’t do well at all — we have some evidence that shows some may not work at all.

Our conclusion is that it’s time to treat overall survival — what has always been a gold standard endpoint — in unrepresentative clinical trials as a surrogate endpoint for survival in the real world. So maybe we should actually have post-marketing commitments and grant only provision approval. Survival is, probably often, merely another surrogate. Like response rate and progression-free survival, as long as it’s conducted in unrepresented populations.

How are you finding OHSU and Portland?

I like being here at OHSU. I’ve been really impressed with my colleagues — across campus there are so many things going on. People at OHSU are working on clever projects. I think the funding for research here allows scientists to treat research as research.

I find a lot of people very like-minded on the topics I research. Pretty much, everyone I’ve met in internal medicine — and people across OHSU really. There are several senior people here who are tremendously supportive.

As for the city of Portland, I love it. I like to ride my bicycle and go on hikes. And to restaurants and the bookstore. But really? I love to binge watch television and movies. Now, Game of Thrones. And, for all time, my favorite show was the Wire.

Jeanette Mladenovic, M.D., M.B.A., M.A.C.P. will retire at the end of 2016. She has served as OHSU’s executive vice president and provost since 2011.

During Mladenovic’s five-year tenure, she has presided over a major realignment of the university. She was recruited to OHSU to help the university plan and construct the Collaborative Life Sciences Building and move OHSU to an interprofessional model of education. She established OHSU as a leader in this arena, removing significant structural obstacles and aligning the education mission across its numerous programs—she oversaw the alignment of 14 different academic program calendars to a single one, she created a uniform student orientation, and she moved the institution to a unified convocation. She also made it possible for students in different programs to take courses across the university, removing a considerable barrier for students.

Mladenovic also transformed the academic mission at OHSU. She led the effort to establish a joint School of Public Health with Portland State University, bringing together two universities with very different cultures. She created a state-of-the-art simulation program by aligning several programs and creating world-class facilities. She initiated a new model for addressing rural health issues by creating the Campus for Rural Health. She consolidated and expanded the reach of OHSU Global, including a unique multi-mission partnership in Thailand, Laos and Myanmar.

Mladenovic has been a champion for students. She established the OHSU Tuition Promise, which protects students from steep rises in tuition during their time at OHSU. She created new financial advising services to reduce debt and better tracking of available scholarship dollars. She oversaw new efforts that significantly boosted student diversity, establishing the Scholars for a Healthy Oregon Initiative and the President’s Fund, both of which recruit and retain diverse students. Student debt has markedly decreased, and OHSU’s tuition is no longer the highest in the nation. She also established several successful pipeline programs.

In addition to her work with students, Mladenovic has strongly advocated for faculty and for more transparent, uniform faculty governance. She established the OHSU Faculty News to keep faculty informed of important institutional news. She made faculty titles and ranks more consistent across the university and recruited and hired a university ombudsman. She created a new vice provost for academic career development specifically to oversee physician scientist training. She promoted the creation and funding of named professorships. And she advocated for a larger voice for faculty in important university decisions, creating the Research Strategic Advisory Council and the Neurosciences Leadership Group, as well as working with the Faculty Senate to expand its role.

Mladenovic guided successful NWCCU accreditation and the revision of OHSU’s strategic plan. She brought together provost operations and university operations into two groups that made strategic operational and budgetary decisions for OHSU, creating savings by aligning functions. She also presided over numerous critical recruitments: regional associate deans for the campus for rural health; deans for the schools of dentistry, nursing, and public health; the director of the Vollum Institute; and vice presidents of human resources, campus safety, and equity and inclusion.

Prior to her work at OHSU, Mladenovic had numerous other leadership roles. An AOA graduate of the University of Washington School Of Medicine, she completed internal medicine residency training at Johns Hopkins Hospital and Stanford University, and her chief residency and hematology fellowship at the University of Washington. She has held leadership roles at the University of Minnesota, University of Colorado, the State University of New York, and the University of Miami. She won several teaching awards throughout her career, and for 18 years directed an NIH-funded laboratory focused on hematopoietic stem cell differentiation. Her clinical activities have included hospital medicine and the care of patients with myeloproliferative diseases.

Nationally, she has served as a member of the Board of Directors of the American Board of Internal Medicine, its Executive Committee, and has chaired the Examination Committees in Internal Medicine. She has also been active as a member of the American Board of Medical Specialties, the Association of Professors of Medicine and its Board, and the American Society of Hematology, and the Accreditation Council for Graduate Medical Education. She has authored more than 90 papers and edited four books. She is also a leading advocate for point-of-care ultrasound in medicine and medical education.

]]>http://www.ohsu.edu/blogs/researchnews/2016/11/11/jeanette-mladenovic-to-retire-as-executive-vice-president-and-provost-ohsu/feed/02017 ICOregon Innovation Showcase registration openhttp://www.ohsu.edu/blogs/researchnews/2016/11/11/2017-icoregon-innovation-showcase-registration-open/
http://www.ohsu.edu/blogs/researchnews/2016/11/11/2017-icoregon-innovation-showcase-registration-open/#commentsFri, 11 Nov 2016 19:27:25 +0000http://www.ohsu.edu/blogs/researchnews/?p=33377Read More]]>OHSU builds collaborations and resources that help investigators translate research innovations into medical products and services. This is one of the ways we improve human health and wellness. Faculty, students, and the public are invited to attend the 2017 ICOregon Innovation Showcase to learn more about available resources that help make this translation happen.

The event will bring together Oregon’s four major research universities, industry, and government to demonstrate how our universities are a driving force in the Oregon innovation ecosystem. Presenters will discuss university innovation and commercialization efforts, innovation resources throughout Oregon, and growing support for innovation at the governmental level. The 2017 ICOregon Innovation Showcase will promote interaction between industry, legislators, and Oregon research universities.

Conference collaborators include OHSU, Oregon State University, Portland State University, University of Oregon, Oregon Translational Research and Development Institute, Oregon Nanoscience and Microtechnologies Institute, and OregonBest.

]]>http://www.ohsu.edu/blogs/researchnews/2016/11/11/2017-icoregon-innovation-showcase-registration-open/feed/0Biomedical Innovation Program – moving innovations to markethttp://www.ohsu.edu/blogs/researchnews/2016/10/21/biomedical-innovation-program-turns-4-marks-success/
http://www.ohsu.edu/blogs/researchnews/2016/10/21/biomedical-innovation-program-turns-4-marks-success/#commentsFri, 21 Oct 2016 20:46:02 +0000http://www.ohsu.edu/blogs/researchnews/?p=33256Read More]]>For research scientists whose technical innovations have the potential to improve patient care, OHSU created the Biomedical Innovation Program. For four years now, BIP has been providing expertise and resources to steward innovations from the laboratory to clinical application through the process of commercialization. The program is a joint effort between Technology Transfer and Business Development and the Oregon Clinical and Translational Research Institute.

Dr. Muschler has been researching novel approaches to detect and treat diseases of the bladder since he joined OHSU in 2011. There are few treatment options for these diseases, and those therapies are ineffective and costly. Dr. Muschler’s laboratory has developed a technology platform that effectively targets early stage tumor cells in the bladder, making possible early detection and treatment.

As a 2015 BIP grant awardee, Dr. Muschler received funding and development, innovation education, project management support, and mentorship. His technology is now much closer to the marketplace.

OCTRI: As a BIP alumnus, who do you see benefiting from the program?

JM: For anyone with an invention that has commercial potential, the BIP program is an excellent mechanism to move it forward and test the waters. There are many benefits. Learning to think like an inventor or an entrepreneur is a valuable education in itself. And the BIP program can connect you to many creative, helpful, and insightful people.

OCTRI: Tell us how your research led you to the BIP.

JM: A research discovery of ours suggested a new method of targeted drug delivery. We filed an invention disclosure with OHSU Technology Transfer & Business Development, and were then looking for ways to quickly continue the work and develop its commercial potential. A colleague suggested OCTRI and the BIP as a source of early stage funding.

OCTRI: How was your experience with the BIP different from that with other funding sources?

JM: First, in preparing our submission for the BIP grant, we were required to provide information that you don’t see in standard grant proposals. These included a market overview for the proposed product and an outline of the path to commercialization. Also, reviewers of the BIP proposals provided commercialization experience that was helpful in guiding the project. Lastly, and most importantly, the BIP continued to support the team after the award was funded. Throughout the course of the grant, the BIP provided support for the project through connections to people with experience in the various steps of commercialization.

OCTRI: How has participating in the BIP helped move your technology forward?

JM: Obviously, the early stage funding has been crucial to keeping the project alive and to advancing the research. By helping me learn the paths to commercialization, the BIP is also helping to plan ahead and efficiently prepare for the next steps in the commercialization without wasting valuable time.

OCTRI: Can you talk about what you have learned from participating in the program?

JM: The BIP has helped me learn the path from research discovery to product commercialization. Through the BIP, with guidance from program staff and interactions with entrepreneurs, I have begun to step out of the “research scientist” mindset and become more comfortable thinking like an inventor and entrepreneur. A product that makes it to market offers many rewards; there’s a lot to gain with little to lose.

The BIP is a partnership between the Oregon Clinical and Translational Research Institute and OHSU’s Office of Technology Transfer & Business Development. Visit the OCTRI funding page for information on the BIP and other opportunities. For more information on OCTRI resources for investigators and research staff, contact the OCTRI Research Navigator.

]]>http://www.ohsu.edu/blogs/researchnews/2016/10/21/biomedical-innovation-program-turns-4-marks-success/feed/0Who’s new at OHSU? Sivaraman Prakasamhttp://www.ohsu.edu/blogs/researchnews/2016/09/30/whos-new-at-ohsu-sivaraman-prakasam/
http://www.ohsu.edu/blogs/researchnews/2016/09/30/whos-new-at-ohsu-sivaraman-prakasam/#commentsFri, 30 Sep 2016 18:19:43 +0000http://www.ohsu.edu/blogs/researchnews/?p=33121Read More]]>Sivaraman Prakasam, B.D.S., M.S.D., Ph.D., is an assistant professor in the Department of Periodontology, OHSU School of Dentistry. In addition to his research program, Prakasam is a clinical educator and a practicing clinician, limiting his practice to periodontics and dental implant placement.

Prakasam and family

Where are you from originally?I was born and raised in India. I got my dental degree there – a B.D.S. as it’s known in India – and as soon as I was done with that, I knew I wanted to pursue research. I went to the Stony Brook University in New York for my Ph.D. and was fortunate to work under the mentorship of Dr. Chris Cutler an innate immunologist and periodontist. This helped shape the direction of my research career. Though I knew I wanted to do research, I found I missed the clinical side of things while I was completing my Ph.D., so I decided to go back and pursue advanced clinical training. I went to Indiana University School of Dentistry and did my periodontal residency for my specialty training. I stayed as a clinical faculty member for another four years. This was sort of an unofficial postdoc. Because of the projects I developed there, I was then able to apply for a position here at OHSU, which is also part research, part clinical. Though there are similarities, I find I have access to a lot more resources here.

What’s the focus of your research?Understanding periodontal disease. The pervading thought on what this disease is that the biofilm or tooth plaque is the primary etiology and that some people are more susceptible to developing a response to it. Also, there are certain bacteria that are commonly associated with disease process. So, one of the things I worked on as a clinical professor at Indiana was salivary diagnostics. I was able to incorporate the focus of my Ph.D. work – innate immunology – but in terms of translational research. The goal was to try and identify salivary markers that we see in periodontal disease. In developing that project, I came across something called Peptidoglycan recognition proteins, a group of innate immune receptors. It’s unique in the sense it’s a secreted receptor that does two things: kill bacteria and modulate inflammation. Up to now, I’ve been studying this receptor mostly in mice models. But my goal is to understand the relevance of this molecule in terms of human diseases, particularly inflammatory diseases like gum disease. In addition to figuring out what role the receptor plays in periodontal disease, I want to see if it can be used as a biomarker for identifying disease.

Another avenue I’m exploring is that this receptor may have a role to play in other systemic diseases. One of the emerging concepts is that oral disease may be a risk factor or causative agent for distant diseases such as cardiovascular disease and diabetes. There are varied hypotheses about the connection between oral health and say, cardiovascular disease. The controversy lies in causality. Are these people who have poor gum health alongside cardiovascular disease, generally prone to reduced immunity or hyper inflammation? Or is it the type or amount of oral bacteria itself that’s the cause?

The cause may, in fact, be direct. There is a large build-up of bacteria when people don’t brush regularly so that when they do brush or have dental work done like a tooth extraction, this can cause the abnormal levels of bacteria to enter the circulation system, which can eventually precipitate changes in the cardiovascular system. Studies have identified traces of these bacteria in atherosclerotic plaque. These are dead oral bacteria that are not supposed to be in the heart but are often found in people who die of cardiovascular disease. These bacteria have also been found in dead fetuses in certain cases of pregnancy that don’t go to term. So, investigators are trying to establish the connection, and one of my goals is to find out if this receptor could be the link. There is some proteomic data that suggest this molecule may be relevant in various systemic inflammatory diseases.

So this is my primary focus of my research, but I also do a lot of small projects. One of them is my work with a collaborator in Iowa – we do a lot of data mining of a health insurance data base, trying to find links between oral diseases and systemic diseases. We’ve published a few papers published from this line of research. I’m also interested in safety. When I was in Indiana, inspired by Atul Gawande’s pioneering work on WHO Surgical Safety checklist, we developed a safety checklist for implant placement, and that’s been published. Though this is not my main research focus, I feel it’s very important work. Most states have very lax laws in terms of who gets to perform what types of procedures. In the case of dental implant placement, a dentist who has taken minimal training (two to three weeks) may be allowed do the same procedure as someone who’s had two or three years’ worth of training. Developing safety protocols is one way to protect the patient and guide inexperienced practitioners.

What do you do when you’re not at work?I read a lot of books, mostly non-fiction, about self-improvement, leadership, and communication. But mostly I spend time with my family. My wife is at home now with our son who’s two and a half, and she’s also an aspiring pastry chef. Trying not to eat pastries keeps me plenty busy!

]]>http://www.ohsu.edu/blogs/researchnews/2016/09/30/whos-new-at-ohsu-sivaraman-prakasam/feed/0Parkinson’s grants awarded to three OHSU researchershttp://www.ohsu.edu/blogs/researchnews/2016/08/03/parkinsons-grants-awarded-to-three-ohsu-researchers/
http://www.ohsu.edu/blogs/researchnews/2016/08/03/parkinsons-grants-awarded-to-three-ohsu-researchers/#commentsWed, 03 Aug 2016 23:12:30 +0000http://www.ohsu.edu/blogs/researchnews/?p=32646Read More]]>The American Parkinson Disease Association announced today, Aug. 3, that it has awarded $1.6 million toward research for the 2016-2017 funding cycle. Three OHSU researchers are among the recipients of this year’s awards.

Vivek Unni, M.D., Ph.D., assistant professor of neurology in the Parkinson Center of Oregon and Jungers Center for Neurosciences Research at OHSU, is the recipient of the prestigious George C. Cotzias Fellowship, named in honor of the scientist who helped develop Levodopa as a treatment for Parkinson’s disease. The fellowship award will support Unni’s research using new imaging approaches to examine the molecular mechanisms of Lewy body pathology-associated death in mouse models of Parkinson’s disease. Specifically, Unni’s lab is working to distinguish between protective and toxic alpha-synuclein protein aggregates which may lead to new treatments to slow Parkinson’s disease progression.

Ian Martin, Ph.D., assistant professor of neurology in the Jungers Center for Neurosciences Research with membership in the Parkinson Center of Oregon, received one of seven of the association’s research grants. The funding will support his research defining key pathogenic mechanisms underlying neurodegeneration in Parkinson’s disease.

Vinita Ganesh Chittoor, Ph.D., a postdoctoral researcher in the Martin lab, was one of only three Post-Doctoral Fellowship Award recipients. Chittoor works on evaluating the influence of diet on LRRK2-mediated toxicity in Parkinson’s disease. (Mutations in LRRK2, an enzyme encoded by the PARK8 gene, are a proven cause of PD.)

The grants are awarded through a competitive application process and reviewed by American Parkinson Disease Association’s scientific advisory board. “The objective…is to invest in the best science,” said David G. Standaert, M.D., Ph.D., John N. Whitaker Professor, chair of neurology, and director, Division of Movement Disorders, University of Alabama at Birmingham, and chairman, scientific advisory board. “As we evaluate these proposals, we focus on funding researchers who are at the start of their Parkinson’s research career and seek to attract the best and brightest minds to work on this important problem. Our aim is to accelerate research and support translational ideas that have the potential to truly improve the quality of life for persons living with PD.”

]]>http://www.ohsu.edu/blogs/researchnews/2016/08/03/parkinsons-grants-awarded-to-three-ohsu-researchers/feed/0Who’s new at OHSU? Raymond Bergan, M.D.http://www.ohsu.edu/blogs/researchnews/2016/07/28/whos-new-at-ohsu-raymond-bergan-m-d/
http://www.ohsu.edu/blogs/researchnews/2016/07/28/whos-new-at-ohsu-raymond-bergan-m-d/#commentsFri, 29 Jul 2016 00:38:49 +0000http://www.ohsu.edu/blogs/researchnews/?p=32581Read More]]>Raymond Bergan, M.D., is an internationally regarded cancer researcher who joined OHSU as head of hematology and medical oncology in the School of Medicine and as associate director of medical oncology for the OHSU Knight Cancer Institute. He is also a practicing clinician who sees patients at OHSU and the Veterans Administration Portland Health Care System.

What brought you to OHSU?My decision to leave Northwestern University and come to OHSU was two-fold. The opportunity to lead the Hematology & Medical Oncology Division was a big draw but I came in large part because of what OHSU is doing for the field. I’m a medical oncologist and have been in drug discovery and therapeutics – that’s my area of focus. I had been at Northwestern for a long time and got to a point where I asked myself “What do I want to do with the rest of my career?” A career I’ve spent helping patients, developing better therapeutics for patients, and I could see where the field was going – toward precision medicine and personalized therapy. So I thought “Do I want to stay [at Northwestern] and wait for the new guidelines to come out or do I want to go and help shape and define those guidelines? I wanted to help move that science forward and felt this was the right place because of what OHSU was doing for cancer, providing a visionary way forward as objectively measured by the Knight Challenge. It’s not about the money per se but about the tools and capabilities it affords and how OHSU is using the money that is significant.

What is the focus of your research?I came to this division because I thought it had huge potential for further advancing therapeutics. What our group does scientifically is to understand why cancer cells move and therapeutically inhibiting that process. The example I often use is, say a woman discovers a lump in her breast and it turns out to be breast cancer. If it’s just that lump, it’s easy to treat and cure using a local therapy such as surgery or radiation or sometimes chemotherapy; if that cancer hasn’t moved, the woman is cured. If, however, that cancer has moved throughout her body, we can treat it but we can’t cure it. The analogy for breast is true for most cancers. The leading cause of death from cancer is metastatic cancer. So how does that cancer go from the original point and move throughout the body? What kills patients is that process of cell movement, so if you can block that process, you can cure people.

There are many things that are attractive about focusing on motility as a therapeutic target. Until recently, no one had actually been able to do it. But we have. We were the first group to successfully therapeutically target pathways in humans that act to inhibit that process. To clarify, we’ve inhibited a pathway inside cells that’s an important driver of that process. We have not yet shown that we can stop cancer cells from moving in patients and thus have not yet demonstrated benefit to patients. So this is the focus of our laboratory. We’re starting out with prostate cancer, but the research isn’t necessarily limited to that. The overall aim is to discover what regulates and controls cell movement or transformation to a metastatic phenotype and then what part of that process can be therapeutically targeted. We’ve taken agents from bench into clinic through phase II trials, and now we’re putting a lot of effort into discovery of a novel class of agents and moving that forward. This is what’s nearest and dearest to my heart in terms of what our group is working on.

Linked to that, I’m also involved in early phase clinical trials. I have a long history in the field of chemo-prevention. At Northwestern, I put together–and served as PI for over a decade–one of only five National Cancer Institute-funded early phase chemoprevention consortia groups. I built the group to 19 institutions, including two in China, and ran a variety of clinical trials. Early phase trials are what you would consider “go – no go” trials for larger, expensive and potentially risky trials. If you have a promising agent and you’ve run it through a Phase I trial and are confident the drug isn’t toxic, you go to the next phase to see if it does anything of use. If it’s an effective chemoprevention agent acting as expected, you would run a trial in humans looking at target cells in the target tissue in the body to see if you get a response. The outcomes of these early stage trials have molecular endpoints that allow you to say, yes, this is worth further investigation because we know that a certain dose given to a targeted cohort exerts the pharmacologic effect we want in the exact organ we want to target. Tamoxifen is an example of a very successful chemoprevention drug that blocks the actions of estrogen, which is effective against tumors that require estrogen to grow.

But say you developed a drug and in early trials, you didn’t get the response you’d anticipated. We wouldn’t just throw the drug out. We would look at it closely and ask “is it a bad drug? Did we not administer the correct dose?” We might be able to rescue the drug if we find it was a case of bad formulation or we didn’t administer the drug properly. So that’s the purpose of this consortium – to run these types of trials which are very complex and require experts in a particular cancer type or methodology, etc. A single research group or institution can’t cover all those bases which is why a consortium is needed. When I came here I had to give up my leadership of the group, which was probably the hardest thing I’ve ever had to do professionally. Ultimately, the award is made to the institution, so it stayed at Northwestern. But I’m still heavily involved. When I came here, I made OHSU a site and I’m now chair of the Eastern Cooperative Oncology Group Prevention Committee.

I’m passionately committed to this work. I think the way we’re going to have the biggest impact on cancer is in early detection and early intervention.

What do you do when you’re not at work?I love Portland. I knew nothing about it prior to coming here other than having read a few things. There’s so much about it that reminds me of home. I grew up in a rural area of upstate New York in a small town, and I spent a lot of time in the woods when I was young. Here I walk to work and when I’m done working, I’m running on a wooded trail right outside my door. I’m happy anywhere and very much liked living in Chicago. However, Chicago is a large city, and it would take you a long time to get out of it. Here, you have a real city with a downtown that’s vibrant, but you can get out of town in half an hour. I’m also currently learning Chinese, I read a lot of biographies, and I have three wonderful kids that I love spending time with.

]]>http://www.ohsu.edu/blogs/researchnews/2016/07/28/whos-new-at-ohsu-raymond-bergan-m-d/feed/0Co-invented by OHSU’s David Huang 25 years ago, OCT technology helps detect and stop blindnesshttp://www.ohsu.edu/blogs/researchnews/2016/07/14/co-invented-by-ohsus-david-huang-25-years-ago-oct-technology-helps-detect-and-stop-blindness/
http://www.ohsu.edu/blogs/researchnews/2016/07/14/co-invented-by-ohsus-david-huang-25-years-ago-oct-technology-helps-detect-and-stop-blindness/#commentsThu, 14 Jul 2016 20:22:01 +0000http://www.ohsu.edu/blogs/researchnews/?p=32519Read More]]>This year marks the 25th anniversary of the invention of Optical Coherence Tomography technology, co-invented by Oregon Health & Science University Casey Eye Institute’s David Huang, M.D., Ph.D., while Huang was a Ph.D. student with James Fujimoto, Ph.D. at Massachusetts Institute of Technology. To commemorate the anniversary, the Association for Research in Vision and Ophthalmology (ARVO) published a special anniversary edition in their journal Investigative Ophthalmology & Visual Science with more than 70 articles.

David Huang, M.D., Ph.D., and his team at the Center for Opthalmic Center for Ophthalmic Optics and Lasers Lab, or COOL Lab, at Casey Eye Institute

OCT is the most commonly used ophthalmic diagnostic technology worldwide, with an estimated 30 million OCT imaging procedures performed every year. The technology has evolved over the past 25 years to help diagnose and treat the most common causes of blindness: age-related macular degeneration, diabetic retinopathy and glaucoma. OCT use continues to grow exponentially in ophthalmology and other medical specialties, including cardiology, dermatology, neurology, and gastroenterology.

OCT has transformed the way ophthalmologists are able to diagnose, monitor and treat devastating eye diseases, and it has advanced drug discovery and development. The technology is particularly suitable for the early detection of glaucoma and macular degeneration, diseases that may cause significant damage prior to the appearance of symptoms. OCT is also widely used for diabetic macular edema, the leading cause of blindness in young patients.

“Dr. Huang’s contribution to the field of ophthalmology has been tremendous and we are very fortunate to have such a brilliant mind here at Casey Eye Institute and in Oregon,” says David J. Wilson, M.D., director of the OHSU Casey Eye Institute and chair of the Department of Ophthalmology in the OHSU School of Medicine. “This anniversary is a perfect opportunity to celebrate OCT as a truly transformative medical technology. Such transformations do not occur often in medicine.”

OCT technology has also evolved over the past 25 years with great advances in imaging speed and quality. Ophthalmologists can now study disease at the microscopic level without biopsy, and with complete patient comfort. For the first time, eye physicians can visualize and measure blood flow in the smallest of blood vessels, without the need to inject contrast agents. Non-invasive visualization and measurement of blood flow gives great insight into the cause and progression of eye disease.

Huang, who was recently ranked the 4th most influential figure in the world of ophthalmology by The Ophthalmologist PowerList 2016, runs the Center for Ophthalmic Optics and Lasers Lab, or COOL Lab, at Casey Eye Institute which includes a team of top scientists from around the world who have been perfecting OCT technology for more than 15 years. Several members of the lab have contributed articles for the special issue in IOVS (see Related Content for links to articles).

The papers published in the ARVO special issue by OHSU faculty were supported by the National Institutes of Health, Research to Prevent Blindness, Optovue, Inc. and the Oregon Clinical and Translational Research Institute.

]]>http://www.ohsu.edu/blogs/researchnews/2016/07/14/co-invented-by-ohsus-david-huang-25-years-ago-oct-technology-helps-detect-and-stop-blindness/feed/0Who’s new at OHSU? Alexey Danilov, M.D., Ph.D.http://www.ohsu.edu/blogs/researchnews/2016/05/24/whos-new-at-ohsu-alexey-danilov-m-d-ph-d/
http://www.ohsu.edu/blogs/researchnews/2016/05/24/whos-new-at-ohsu-alexey-danilov-m-d-ph-d/#commentsTue, 24 May 2016 16:58:40 +0000http://www.ohsu.edu/blogs/researchnews/?p=32078Read More]]>Alexey Danilov, M.D., Ph.D., is an assistant professor of medicine (hematology and oncology), OHSU School of Medicine, and member of the Knight Cancer Institute. He focuses on treating and diagnosing patients with chronic lymphocytic leukemia (CLL) and various lymphomas. He has been at OHSU for a year, arriving in October 2014.

Alexey Danilov, M.D., Ph.D.

Where are you from originally?I’m originally from Russia, but I did most of my training in the New England area of the U.S. I arrived in 2001 and completed my residency in medicine at Brown University and then followed that on with a fellowship at Tufts Medical Center in Boston. I then moved to Dartmouth as my wife was finishing her studies there, so I ended up as a senior fellow in Murray Korc’s lab working on pancreatic cancer. A year after I arrived, Dr. Korc left. Luckily, I received some support to work independently. This presented an opportunity to do what I wanted to do. I continued with my clinical and research interest in B-cell malignancies, and, with support of my clinical colleagues, I set up my own independent translational program in chronic lymphocytic leukemia (CLL).

What brought you to OHSU?I moved here for a variety of reasons. Some were personal – my wife is a pathologist and was able to find a position at the VA. But more importantly, I found a many like-minded people here, people who want to bring novel therapies into the clinic. As a physician-scientist, I am eager to bring novel therapies into clinical world. So, I constantly operate at the interface between the lab bench and the clinic, meaning that I work with drugs in the pre-clinical setting and usher them into early-stage clinical development. OHSU is one of the institutions that is good at this kind of work. This is a very complicated setting, requiring depth of both basic and translational science, and OHSU has it figured out. Therefore, this was just the right place for me.

What got you interested in this particular line of research?I was drawn to hematology oncology because of the high translational relevance of the work. It’s important to me that I work with primary human samples, so that my work is immediately relevant to the clinic. In CLL and some lymphomas, there is access to biologic material which can be used in translational studies. This is very different than studying solid tumors where access to diseased tissue may be very limited. Not only do lymphomas interest me clinically, the ability to work with lymphoma samples provides immediate relevance to my work in the lab. Another unique feature of working with blood cancers is the ability to make diagnosis on the slides. While I’m not a pathologist, I have the benefit of seeing the actual patient and that very tangible visual connection with the patient’s disease.

My specific focus in studying lymphoma is to target the leukemia cell interaction within the cell’s micro-environment. At the time I entered the field, there were a couple of new agents that targeted certain pathways, mostly the B-cell receptor signaling pathway. However, our team discovered that in addition to this pathway, there are a multitude of extraneous signals which support the life of a malignant B-cell in its niche – its niche being the lymph node of the bone marrow, not necessarily in the blood. So we have modeled the lymph node micro-environment in vitro and screened for different survival strategies of the neoplastic B-cell to identify what can be targeted in these micro-environmental conditions. Of particular interest to my team was targeting the NF-kB transcription factor, which is one of the key transcription factors induced by multiple soluble factors in the micro-environment. NF-kB works independent of B-cell signaling, the pathway of which is the primary target of current approved drugs.

What specific area of research are you working on now?We’ve identified the new strategies outside the B-cell signaling pathways – which I describe above – and our data suggest that not only can the new strategies work by themselves, but they can work as strong sensitizers to the drugs that are already available. So we’re looking into the details of how the NF-kB pathway can be targeted. There are multiple complexities in terms of how the NF-kB pathway is induced. In addition, there are several branches within the pathway, so we’re trying to figure out which are important and which aren’t. We have a number of clinical trials underway for patients with CLL and lymphoma, some of which I based on the pre-clinical work performed by my team. The trials provide good options for folks who have just been diagnosed or those who have progressed through different treatments that haven’t been completely successful.

What do you do when you’re not at work?Let me start by saying that I’ve lived in many places: Central Russia, throughout New England, and I’ve never been as happy as I am living in Portland. There is just so much to do – too many distractions actually. It’s almost too much for one place! We love the hiking, skiing, food, theater, biking, great music scene. This is also a great area for kids – from OMSI and Playdate PDX to kid-friendly hikes – almost too much of a good thing.

]]>http://www.ohsu.edu/blogs/researchnews/2016/05/24/whos-new-at-ohsu-alexey-danilov-m-d-ph-d/feed/0Philip Copenhaver, Ph.D., receives 2016 women’s health Circle of Giving granthttp://www.ohsu.edu/blogs/researchnews/2016/05/20/philip-copenhaver-ph-d-receives-2016-womens-health-circle-of-giving-grant/
http://www.ohsu.edu/blogs/researchnews/2016/05/20/philip-copenhaver-ph-d-receives-2016-womens-health-circle-of-giving-grant/#commentsFri, 20 May 2016 20:51:08 +0000http://www.ohsu.edu/blogs/researchnews/?p=32065Read More]]>The OHSU Center for Women’s Health Circle of Giving, a group of philanthropic women who pool and target their resources to advance women’s health research at OHSU, selected Philip Copenhaver, Ph.D., from the department of Cell, Developmental & Cancer Biology to receive their annual grant. The grant will support Dr. Copenhaver and his collaborators to investigate the potential of STX, a novel selective estrogen receptor modulator, to have long-term protective effects on neurons in the brain. Ultimately, his research will be used to see whether STX can be used as an alternative to estrogen use in preventing dementia and Alzheimer’s Disease.

The Circle of Giving grant is focused exclusively on OHSU researchers who wish to launch new ideas and innovations in a broad range of women’s health issues. The next grant cycle will begin in December 2016. Please contact Casey Conrad for more information about submission requirements.

I would like to invite you to join me in celebrating OHSU Research Week, May 2-6, 2016, our annual celebration of research at Oregon Health & Science University. More than 200 OHSU researchers will be presenting their latest findings throughout the week. I encourage you to show your support by attending talks and poster sessions. Many of the presenters are trainees, the future of the biomedical research workforce.

In addition to OHSU presenters, we have an exceptional lineup of visiting experts, including Charles Rafferty, Ph.D., a recently retired review branch chief at the National Institutes of Health. On Tuesday, May 3, at 12 p.m. in the OHSU Auditorium, Dr. Rafferty will lead a simulated study section meeting to review two actual NIH grant applications, offering an inside look at the NIH grant review process.

The work of our research scientists, students, postdocs, and staff is the foundation underlying OHSU’s success as an academic health center. I hope you will help me celebrate their achievements by attending Research Week events.

Sincerely,

Dan Dorsa, Ph.D.
Senior Vice President for Research, OHSU

]]>http://www.ohsu.edu/blogs/researchnews/2016/04/26/youre-invited-to-research-week-2016/feed/0Eric Gouaux’s serotonin transporter research featured by NIHhttp://www.ohsu.edu/blogs/researchnews/2016/04/19/eric-gouauxs-serotonin-transporter-research-featured-by-nih/
http://www.ohsu.edu/blogs/researchnews/2016/04/19/eric-gouauxs-serotonin-transporter-research-featured-by-nih/#commentsTue, 19 Apr 2016 20:18:47 +0000http://www.ohsu.edu/blogs/researchnews/?p=31809Read More]]>Recent findings by Vollum Institute senior scientist, Eric Gouaux, Ph.D., and team that reveal the molecular structure of the human serotonin transporter, are getting a lot of attention from the biomedical community and the media. Gouaux’s study was featured in NIH Research Matters, the online publication that highlights groundbreaking NIH-funded discoveries. The article, “Serotonin transporter structure revealed,” discusses the innovative technique developed by the team that allowed them to use X-ray crystallography to capture a 3-D image of the protein. “The technique yielded a detailed molecular map of the human serotonin transporter’s structure… The researchers could also see where genetic variations associated with various psychiatric disorders are located in the transporter. Knowing the structure of the transporter can help researchers gain insights into the molecular causes of these disorders and of antidepressant treatment resistance.”

]]>http://www.ohsu.edu/blogs/researchnews/2016/04/19/eric-gouauxs-serotonin-transporter-research-featured-by-nih/feed/0Volunteer as a presentation judge at Research Week!http://www.ohsu.edu/blogs/researchnews/2016/04/15/volunteer-as-a-presentation-judge-at-research-week/
http://www.ohsu.edu/blogs/researchnews/2016/04/15/volunteer-as-a-presentation-judge-at-research-week/#commentsFri, 15 Apr 2016 18:25:57 +0000http://www.ohsu.edu/blogs/researchnews/?p=31774Read More]]>Research Week 2016 is fast approaching and we need your help! We are looking for 51 faculty, postdocs, and research staff to serve as judges for students and postdocs who are presenting talks and posters during Research Week, May 2-6. For each session for which you sign up to judge, you’ll be asked to evaluate a maximum of four student presentations (either oral or poster). Visit the sign-up page for a full listing of session dates, times, and research topics that need coverage. To sign up, check the box for the session you’re interested in and click “submit”–once you get into the tool, you’ll be able to see full details. You can also view the session schedule to see which research presentations fit your expertise.

This is a great opportunity to provide valuable feedback to students and postdocs, and to learn more about the wide-ranging, innovative research taking place here at OHSU.

We kindly ask that you register as soon as possible so we can fill any gaps before the main event. Thank you for contributing to a successful Research Week 2016!

]]>http://www.ohsu.edu/blogs/researchnews/2016/04/15/volunteer-as-a-presentation-judge-at-research-week/feed/0The three laws of communication: Jean-Luc Doumont lecture, Apr. 7http://www.ohsu.edu/blogs/researchnews/2016/03/18/the-three-laws-of-communication-jean-luc-doumont-lecture-apr-7/
http://www.ohsu.edu/blogs/researchnews/2016/03/18/the-three-laws-of-communication-jean-luc-doumont-lecture-apr-7/#commentsFri, 18 Mar 2016 19:45:49 +0000http://www.ohsu.edu/blogs/researchnews/?p=31537Read More]]>Useful as each of them can be, a large body of tips and tricks is impossible to remember, at least in a practical, usable way, unless it is structured into a balanced, meaningful hierarchy. In this talk, Jean-luc Doumont, Ph.D., proposes and illustrates three simple yet solid ideas that lead to more effective communication and that underpin every other guideline: easy to remember, readily applicable, and always relevant—in short, valuable for the rest of your life.

An engineer and Ph.D. in applied physics, Jean-luc Doumont is acclaimed worldwide for his no-nonsense approach, his highly applicable, often life-changing recommendations on a wide range of topics, and Trees, maps, and theorems, his book about “effective communication for rational minds.”

]]>http://www.ohsu.edu/blogs/researchnews/2016/03/18/the-three-laws-of-communication-jean-luc-doumont-lecture-apr-7/feed/3Prep for Research Week 2016: How to write an abstract workshop, Feb. 26http://www.ohsu.edu/blogs/researchnews/2016/02/17/prep-for-research-week-2016-how-to-write-an-abstract-workshop-feb-26/
http://www.ohsu.edu/blogs/researchnews/2016/02/17/prep-for-research-week-2016-how-to-write-an-abstract-workshop-feb-26/#commentsWed, 17 Feb 2016 22:37:51 +0000http://www.ohsu.edu/blogs/researchnews/?p=31375Read More]]>Whether you’re clueless when it comes to writing an abstract, or an expert looking to refine your skills, join us for a skill development workshop about how to write and abstract in preparation for Research Week. The workshop will be led by David Jacoby, M.D., professor of medicine, and chief, pulmonary and critical care.

]]>http://www.ohsu.edu/blogs/researchnews/2016/02/17/prep-for-research-week-2016-how-to-write-an-abstract-workshop-feb-26/feed/0Marc Freeman to join Vollum Institute as directorhttp://www.ohsu.edu/blogs/researchnews/2016/02/12/marc-freeman-to-join-vollum-institute-as-director/
http://www.ohsu.edu/blogs/researchnews/2016/02/12/marc-freeman-to-join-vollum-institute-as-director/#commentsFri, 12 Feb 2016 19:07:33 +0000http://www.ohsu.edu/blogs/researchnews/?p=31572Read More]]>Marc Freeman, Ph.D., Howard Hughes Medical Investigator, and professor and vice chair of the Department of Neurobiology at the University of Massachusetts Medical School, will join OHSU as director of the Vollum Institute.

Dr. Freeman received his M.Phil. and his Ph.D. in biology from Yale University. He carried out his doctoral training in the laboratory of John Carlson at Yale, where he studied Drosophila olfaction. He then trained as a postdoctoral associate with Chris Q. Doe at the University of Oregon, studying embryonic neurogenesis with a particular focus on glial development and neuron-glia interactions.

He went on to start his own laboratory in the Department of Neurobiology at the University of Massachusetts Medical School in 2004, studying glia-neuron interactions in the healthy and diseased brain. Dr. Freeman was an Alfred P. Sloan Research Fellow (2005), an Early Career Scientist with the Howard Hughes Medical Institute (2009-2013), and recently received the Javits Neuroscience Investigator Award from NINDS. He is also chair of the NINDS Cell and Molecular Biology of Glia study section.

He will transition to OHSU later this year. Stay tuned for more information.

]]>http://www.ohsu.edu/blogs/researchnews/2016/02/12/marc-freeman-to-join-vollum-institute-as-director/feed/0Five OHSU researchers among the most influential scientific minds of 2015http://www.ohsu.edu/blogs/researchnews/2016/01/20/five-ohsu-researchers-among-the-most-influential-scientific-minds-of-2015/
http://www.ohsu.edu/blogs/researchnews/2016/01/20/five-ohsu-researchers-among-the-most-influential-scientific-minds-of-2015/#commentsWed, 20 Jan 2016 17:51:04 +0000http://www.ohsu.edu/blogs/researchnews/?p=31179Read More]]>Thomson Reuters has named five OHSU researchers among their list of the world’s most influential scientific minds 0f 2015. The annual list comprises authors whose work has consistently wielded great influence in the form of citations from fellow scientists. This year’s list includes five OHSU researchers from three different disciplines:

Social Sciences

Susan Norris, M.D., M.P.H., formerly of OHSU and now with the World Health Organization, is also named.

The list was compiled by analyzing citation data over an 11-year period (2003-2013), and identifying those who published the greatest number of highly cited papers in that time frame. Highly cited papers rank in the top 1% of the citation distributions of comparable papers, matched for field and age.

]]>http://www.ohsu.edu/blogs/researchnews/2016/01/20/five-ohsu-researchers-among-the-most-influential-scientific-minds-of-2015/feed/0Murine CRISPR/Cas9 pilot program updateshttp://www.ohsu.edu/blogs/researchnews/2015/12/08/murine-crisprcas9-pilot-program-updates/
http://www.ohsu.edu/blogs/researchnews/2015/12/08/murine-crisprcas9-pilot-program-updates/#commentsTue, 08 Dec 2015 23:06:36 +0000http://www.ohsu.edu/blogs/researchnews/?p=30960Read More]]>CRISPR/ Cas9 gene editing is rapidly becoming the state of the art for mouse genome engineering. During the last year, the OHSU Transgenic Mouse Models Core has successfully used this technology to generate both targeted gene knock-outs and point mutation knock-ins for its clients.

The Transgenic Mouse Models Core has revised its CRISPR pricing structure for 2016. Non-homologous end joining-based gene knock-outs for OHSU investigators will be $2100 per project (150 injections), with the user responsible for design and validation of targeting strategy. CRISPR-based point mutation projects will temporarily remain at $1500 until this approach is considered routine. The same pricing applies for projects aimed at inserting larger fragments of DNA such as epitope tags, loxP recognition sites, fluorescent proteins, or similar insertion strategies. Exploratory technique pricing requires additional consultation with the core for approval.

A new, streamlined option has been added for users with less molecular expertise or resources for knockout. In this case, the user simply indicates the target gene and desired deletion region. Design and validation of the gRNA is conducted through the core, and the user will be presented with candidate gene-deleted offspring to be confirmed by the end user. The price for this service will be around $4400.

These services qualify for the support programs offered by the Office of the Senior Vice President for Research ($10,000) and the School of Medicine ($5,000).

Inquiries should be sent to University Shared Resources Program Director, Andy Chitty.

]]>http://www.ohsu.edu/blogs/researchnews/2015/12/08/murine-crisprcas9-pilot-program-updates/feed/0Who’s new at OHSU? Marina Guizzetti, Ph.D.http://www.ohsu.edu/blogs/researchnews/2015/11/10/whos-new-at-ohsu-marina-guizzetti-ph-d/
http://www.ohsu.edu/blogs/researchnews/2015/11/10/whos-new-at-ohsu-marina-guizzetti-ph-d/#commentsTue, 10 Nov 2015 20:03:47 +0000http://www.ohsu.edu/blogs/researchnews/?p=30802Read More]]>Marina Guizzetti, Ph.D., is an associate professor in the Department of Behavioral Neuroscience at OHSU and a research biologist with the Portland VA Health Care System. Her research focuses on the neurodevelopmental effects of alcohol on the developing brain, specifically looking at Fetal Alcohol Spectrum Disorders.

Marina Guizzetti and family

Where are you from originally?I’m from northern Italy and also where I was educated. I got my degree at the University of Pavia just south of Milan. This is the same university from which Camillo Golgi, who won the Nobel Prize in 1906 for his work on the structure of the nervous system, graduated and worked for most of his career. Among other things, he discovered a technique for staining brain tissue he called “reazione nera” (black reaction) that’s still in use today. I completed my Ph.D. at the University of Milan. In 1994, I moved to Seattle to do my postdoc at the University of Washington. I was there for six years as a postdoc and another 10 years as a research scientist. I then moved to the University of Illinois in Chicago to take a position as associate professor and was there for about five years before coming to OHSU in February.

What brought you to OHSU?
My predecessor in this position retired, and I was approached by the VA and OHSU’s Department of Behavioral Neuroscience to replace her, as our research was well aligned. The department has a very large program on alcohol research, and I have been working in this field since I came to the U.S. in 1994. It was a good fit.

What is the primary focus of your research?Since my time at the University of Washington, my work has focused on the cellular mechanisms involved in the neurodevelopmental effects of alcohol on the developing brain underlying Fetal Alcohol Spectrum Disorders, or FASD. In utero alcohol exposure causes a wide range of developmental effects including Fetal Alcohol Syndrome at the most extreme end of the spectrum.

While I’m now working in the Department of Behavioral Neuroscience, I’m actually a cell biologist by training and love the mechanistic aspect of neuroscience research. I’m particularly interested in glial cells and their role in modulating neuronal development and function. The word glia is derived from ancient Greek and literally means “glue.” When these cells were first discovered, they were thought to do nothing other than keep neurons in place. But in the last 20 years, we’ve come to realize that they play a major role in brain physiology and pathology and are involved in a number of functions that, in the past, were considered neuron functions. Genomic studies of neurological disorders show that many of the genes that are mutated and change are glial genes. So, big changes occur in these cells, and it appears they have a role in the pathology of alcoholism and other conditions.

I study one particular glial cell type, astrocytes, that we now know are involved in the regulation of neuronal development. When we characterized the proteins released by these cells by proteomics, we identified many extracellular matrix proteins. During brain development, astrocytes release both extracellular matrix components that inhibit neuronal development (i.e. axonal and dendrite extensions) in certain directions and extracellular matrix components that promote neuronal development in other directions in temporary and spatially specific patterns. These components contribute to the formation of the proper network architecture. Later, in order for synaptogenesis to occur, astrocytes modify the factors they release. What we found is that when you treat the astrocytes with alcohol, you have a dysregulation of proteins being released, leading to inhibited neuronal development. Furthermore, when alcohol is removed from the astrocytes after treatment, the dysregulation persists. Astrocyte-mediated dysregulation of neuronal development has been reported also in other neurodevelopment disorders such as Down syndrome, fragile X syndrome, and Rett syndrome. The specific effects are different, but dysregulation of astrocyte function is common to several neurodevelopmental disorders.

For a diagnosis of FAS, growth retardation, neurodevelopmental dysfunction, and specific facial dysmorphic characteristics need to be present. However, even in the absence of these facial characteristics, heavy prenatal alcohol exposure can cause permanent cognitive and behavioral dysfunction. We know that alcohol affects brain development throughout gestation. We also know that binge drinking can be more destructive than lower levels of constant exposure. When alcohol exposure is milder or happens later in pregnancy, some of the physical characteristics associated with FAS may not be present or may disappear with age, making FASD particularly difficult to diagnose. While FAS is an official medical diagnosis, FASD is not. This means people suffering from it aren’t always eligible for government assistance, and yet these individuals may be severely impacted. Many of them have low cognition, extremely poor judgment, a tendency to abuse alcohol or other substances, and sadly, sexual disinhibition, which leads to pregnancies in young women who also drink. And the cycle continues. It’s very sad.

Does your research address treatment or prevention?I have a program that looks at supplementation of choline during alcohol exposure in the rodent equivalent of the third trimester of human gestation to see if it improves outcomes as other studies have indicated. I’m looking at the mechanisms by which choline may improve the effects of alcohol on the fetus. We have shown that ethanol affects DNA methylation in astrocytes. In this study, we explore whether epigenetic changes in DNA methylation induced by ethanol in astrocytes can lead to reduced neuronal structural plasticity and behavioral anomalies. Choline can modulate the epigenetic processes of DNA and histone methylation, but also it is a common dietary supplement that is safe to take by pregnant women and infants/children. Therefore, choline represents an ideal potential treatment to prevent and/or ameliorate the effect of excessive alcohol drinking during gestation.

What do you like to do for fun?Well, work and family take a lot of time. What we have been enjoying is taking small trips around Oregon. We like to cook, and my favorite thing to make, because I like to eat it, is homemade gnocchi. So, we like to hike and we like to eat. My husband wants to try a new restaurant every week because the food in Portland is so fantastic. We’re delighted to be here!

]]>http://www.ohsu.edu/blogs/researchnews/2015/11/10/whos-new-at-ohsu-marina-guizzetti-ph-d/feed/0Announcing Data Science forums for OHSU researchershttp://www.ohsu.edu/blogs/researchnews/2015/10/30/announcing-data-science-forums-for-ohsu-researchers/
http://www.ohsu.edu/blogs/researchnews/2015/10/30/announcing-data-science-forums-for-ohsu-researchers/#commentsFri, 30 Oct 2015 19:30:54 +0000http://www.ohsu.edu/blogs/researchnews/?p=30717Read More]]>Do you have an opinion about the future of data science or research informatics at OHSU? If so, this is your chance to provide input for OHSU’s new data science initiative. OHSU will be investing in clinical and research informatics in the next several years, and the institution wants to hear from you about what is needed to succeed.

You’re invited to attend a series of three, 90-minute forums across campus to solicit input from the research community. Tim Burdick, chief clinical research informatics officer, will facilitate structured exercises to create a vision for the future of OHSU data science and research informatics. This vision will then be used to inform the strategy and investments.

The forums are open to all members of the research community and are scheduled for the following dates and times:

Small group brainstorming session: What informatics support would you want in the future to facilitate your research?

Small group report out: Share with the other groups in attendance what your group envisions for the future

Discussion

There is no need to RSVP. You can simply show up at a session prepared to participate! Snacks and drinks will be served, and OHSU merchandise will be provided for all participants.

]]>http://www.ohsu.edu/blogs/researchnews/2015/10/30/announcing-data-science-forums-for-ohsu-researchers/feed/0OHSU Presidential Bridge Funding applications due Dec. 31http://www.ohsu.edu/blogs/researchnews/2015/10/29/ohsu-presidential-bridge-funding-applications-due-dec-31/
http://www.ohsu.edu/blogs/researchnews/2015/10/29/ohsu-presidential-bridge-funding-applications-due-dec-31/#commentsThu, 29 Oct 2015 18:27:48 +0000http://www.ohsu.edu/blogs/researchnews/?p=30683Read More]]>The Office of the Senior Vice President for Research has released its call for proposals for the FY16 winter OHSU Presidential Bridge Funding Program. Bridge funding is available for established investigators threatened by an imminent lapse in research support. Investigators can request up to $50,000 in funding for one year to help bridge them while they generate data to restore funding. Up to 6 awards will be made this funding cycle.

Awards will be made only to OHSU investigators. The PI must be an independent scientist. Independence is defined by: rank at the level of assistant professor or above; committed institutional support such as space and salary; a track record of first authored or senior authored publications; a recent history of federal (or similar) funding; and imminently planned or pending application for funding on a national level. Postdoctoral fellows and similar trainees are not eligible to apply.

]]>http://www.ohsu.edu/blogs/researchnews/2015/10/29/ohsu-presidential-bridge-funding-applications-due-dec-31/feed/0Who’s new at OHSU? Khaled Tolba, M.D.http://www.ohsu.edu/blogs/researchnews/2015/10/15/whos-new-at-ohsu-khaled-tolba-m-d/
http://www.ohsu.edu/blogs/researchnews/2015/10/15/whos-new-at-ohsu-khaled-tolba-m-d/#commentsThu, 15 Oct 2015 23:05:15 +0000http://www.ohsu.edu/blogs/researchnews/?p=30576Read More]]>Khaled Tolba, M.D., is an assistant professor of medical oncology, division of hematology-oncology and has been at OHSU since January. His research focuses on developmental therapeutics and early clinical trial development for lung, and head and neck cancer. In addition to helping facilitate access to the latest clinical trials, Tolba also cares for patients with these cancers, providing tailored treatments including immune therapy and molecular targeted therapies.

Where are you from originally?I was born, raised, and educated in Cairo, Egypt. But I also completed part of my medical school training at McGill University in Montreal, Canada. I then did a couple of years of research at Hoffmann-La Roche, in Basel, Switzerland and Milan, Italy. After that, I completed my residency at Tufts University in Boston and my fellowship at the University of Rochester. I stayed at the University of Rochester as faculty for nearly four years and then moved to take a position in lung cancer at the University of Miami where I stayed for about 12 years until I came to OHSU.

Khaled Tolba, M.D.

What brought you to OHSU?My predecessor in this position moved to the University of Miami so that’s how I found out about the opportunity. I was very familiar with OHSU because I had been following the work of Brian Druker. My area of interest is in signal transduction in lung cancer, and there’s a lot of overlap between what people are trying to do in lung cancer today and what Dr. Druker did 20 years ago in Chronic Myeloid Leukemia. In a sense, OHSU is at the epicenter of targeted therapy, so when this opportunity came up, I didn’t hesitate to take it.

I started my career as a physician-scientist; my lab worked on tumor immunology and signal transduction. Today, I’m a full-time clinician; I see most of the head and neck and lung cancer patients at OHSU. My time is divided 50/50 between research and patient-care activities. My research focuses on early phase clinical trial development and I have a particular interest in the development of combination targeted therapy for lung cancer.

What drew you to lung cancer research?I was attracted to lung cancer as an example of a very complex disease. When I started working in the field about 15 years ago, there were no effective treatments, no rationally thought-out therapies. It was a fairly depressing field to get into, but it was also a very complex problem that I wanted to make a contribution to. What we knew back then was sort of naïve and pedestrian compared to what we know about lung cancer today. I would say the beginning of most of the work I do now began with the introduction of the first targeted agent in lung cancer, a small molecule inhibitor of the epidermal growth factor receptor, gefetinib. This also coincided with the publication of the human genome by the Human Genome Project in 2001. The two events didn’t seem related at the time but in hindsight, the field couldn’t have moved forward the way it did building on one without the other. This sequencing technology developed for the Human Genome Project opened the door for us to sequence a tumor, understand what mutation is present, and then ask questions about that specific mutation.

Another significant development that changed the field of lung cancer research was the development of Next Generation Sequencing, or NGS, high throughput sequencing that allowed us to apply this knowledge to everyone with lung cancer. The Human Genome Project cost roughly $1 billion to sequence five or six people. So even if the cost of traditional sequencing comes down, you’re still looking at prohibitive cost associated with traditional sequencing methods. There are roughly 225,000 people diagnosed with lung cancer every year, so you’re never going to be able to apply something that expensive across the vast population with lung cancer. NGS was the great equalizer. It was sort of like Henry Ford developing the model T. Mass production allowed the middle class to purchase something that only the wealthy had been able to afford. That’s what NGS did for lung cancer patients. Lastly, the development of small molecules that can block certain signaling pathways made precision medicine a reality.

These developments were seminal because without finding the exact mutation, you can’t find the right treatment. You can’t test different hypothesis and treatment paradigms. Now, almost anyone diagnosed with lung cancer can have their tumor molecularly profiled to find their mutation driver. Then we can determine what agent can be applied to that tumor. Even though it’s not 100 percent effective- we don’t have treatment for every tumor type we identify – it really revolutionized the field. So much so that the most rapidly growing segment of lung cancer research is targeted therapy and small-molecule therapy that can inhibit signaling pathways. This is where the field is moving, and this is where my focus is in clinical research.

How does your research specifically tie in with these advancements?My focus is on signal transduction – what makes a tumor cell behave the way it does? What makes it susceptible to certain drugs? My goal is to understand this process, a roadmap of what happens inside the tumor cell, and use that to identify targets to kill or stop cancer from growing. This type of investigation allows us to identify the “Achilles heel” of the tumor cell – what is its weakest point or pathway? Then we test different targeted therapies or specific molecules that will cripple that pathway in the tumor cells, and, for the most part, spare the rest of the body.

Until 10 or 15 years ago, the only available treatment was chemotherapy, which is a bit like killing a mosquito with a hammer and unfortunately, we were not that good at using the hammer either. If you’re lucky, you hit the mosquito but more often than not, you end up doing more damage than good. The new thinking is to use precision targeting – a new drug that attacks this vulnerable pathway in the tumor cell and spares the rest of the body.

My work is to develop new clinical trials that test this concept of targeted therapy. I have a couple of trials I’ve been working on for several years that will open here at OHSU in the near future. Both involve identifying these vulnerable pathways and testing various molecules to see if they disrupt the pathways. We are also testing different regimens for delivery of these molecules to see if there are ways to make them more effective at killing tumor cells.

For a very long time, people thought of lung cancer as a single entity and attributed it mostly to smoking. What we know now is that lung cancer is actually an umbrella term for nearly 25 different diseases or cancer types. They are different diseases that happen to share a single location – the lung. If you do a detailed sequencing of “lung cancer,” you’ll find a couple dozen different lung cancers. It’s similar to how people thought of the stars a thousand years ago – they’re all bright objects in the sky and it was only when we developed cutting edge telescopes that we were able to sort out these objects into planets, stars, and galaxies.

In order to effectively treat lung cancer we must put aside the old way of thinking and start looking at lung cancer’s subsets and apply treatments specific to those subsets. Lung cancer is the poster child for the precision medicine approach. The ability to be precise not only has bearing on the treatment for patient but also on cost. These drugs are very expensive, and using the wrong drug in the wrong patient is not only potentially fatal for the patient but also a huge waste of money.

What do you like to do for fun?I really like to cycle, and I do a lot of that on the weekends. Also, my family just joined me here in Portland this summer so I enjoy spending time with my children who are now 6, 8 and 11. They’re involved in archery. They just finished a camp where they honed their skills – skills I’m sure will come in very handy.

]]>http://www.ohsu.edu/blogs/researchnews/2015/10/15/whos-new-at-ohsu-khaled-tolba-m-d/feed/0OHSU Casey Eye Institute researchers shed light on retinal neural circuitryhttp://www.ohsu.edu/blogs/researchnews/2015/10/08/ohsu-casey-eye-institute-researchers-shed-light-on-retinal-neural-circuitry/
http://www.ohsu.edu/blogs/researchnews/2015/10/08/ohsu-casey-eye-institute-researchers-shed-light-on-retinal-neural-circuitry/#commentsThu, 08 Oct 2015 18:26:13 +0000http://www.ohsu.edu/blogs/researchnews/?p=30492Read More]]>Researchers from the Casey Eye Institute, graduate student Benjamin Murphy-Baum and co-investigator W. Rowland Taylor, Ph.D., have deciphered how neurons in the eye detect the orientation of objects in the visual field. The paper detailing their findings, “The synaptic and morphological basis of orientation selectivity in a polyaxonal amacrine cell of the rabbit retina,” was published in the Sept. 30, 2015, edition of The Journal of Neuroscience.

Vision is a complex sensory system triggered by light energy that’s converted to electrical signals which are then controlled and made more precise by synaptic interactions within retinal neurons. In this study, the research team set out to better understand the computational power of the retina to determine what we see. They discovered a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation due primarily to the elongated shape of the neuron’s branched projections. In simple terms, the shape of a population of specific neurons is elongated, and if the image of the object in the eye is aligned with the neuron, it will respond more strongly. In addition, integration of visual signals in the receptive field center suppress responses to small objects and fine textures, resulting in improved sensitivity to larger objects.

These findings lay the foundation for learning how the orientation signals are conveyed to the optic nerve for transmission to the brain. Expanded knowledge of this system brings scientists one step closer to developing treatments and therapies for patients with retinal degenerative diseases such as macular degeneration and retinitis pigmentosa.

Where are you from and where did you study?I’m from Ohio originally, but I attended the University of Oregon as an undergraduate because my family had moved here. I went to UC Davis for graduate school and earned my Ph.D. in nutrition science there. While at Davis, I studied with a nutritional geographer, Louis Grivetti. He had very broad interests in nutrition. As an example, he would go into caves and look at drawings and try to understand what people ate during the time the drawings were made. Drawings of children might indicate nutrient deficiencies and malnutrition with renditions of say, bowed legs or tummies that stuck way out, but the figures were otherwise very skinny. My work with him looked at social and cultural influences on what we eat and the health consequences of those choices. I am still very interested in this type of research, and because it’s a process-oriented interest, it can be applied to any group of people anywhere.

How did you get involved in nutrition research for people with disabilities?I started working in disability about 15 years ago and sort of fell into it by happenstance, as often happens. What really drew me to the work is unraveling the complex influences on the food habits and nutrition-related behavior of adults who were living with disability and how that played out for their health, as well as independence and quality of life. Adults with intellectual and developmental disabilities are at higher risk for nutrition-related secondary conditions—a secondary condition being something that’s preventable and doesn’t necessarily have anything directly to do with the disability but the disability puts these individuals at risk for the condition. For example, obesity rates are higher in this population, but obesity is not a comorbidity of disability. However, adults with disability are at higher risk due to many influences, which are complicated and interwoven. Contributing factors can include support staff or care providers for those who need assistance with food-related tasks. These care providers bring all of their food issues and biases with them when they assist with purchasing and preparing food. Also, social and media influence seems to be greater with this population. They may eat more junk food, and part of that is about education, but part of it’s about being influenced. The consequences are such that there’s a narrower margin of health for these folks. The ramifications can be dramatic for a person who has a disability who becomes obese. They may have to move into a higher support setting and lose their independence as adults. Imagine losing your independence when you’re 35 years old and when it is entirely preventable? I get very worked up over the injustice of this; I am very mission oriented about it.

Where were you before coming to OHSU?
Before coming to OHSU about a year ago, I was at the University of Montana in Missoula and ran an independent, grant-funded research lab there for 18 years investigating these issues. I was affiliated with the University Center for Excellence in Developmental Disabilities (UCEDD) there and had a faculty appointment in the School of Public and Community Health Sciences.

What brought you to OHSU?The UCEDD director position opened up here and it was both a fabulous opportunity for me and a place I felt I could make a difference. Most states only have one UCEDD, but Oregon has two. Here at OHSU, we’re focused on health, and the UCEDD in Eugene is focused on disability in education. We’re fortunate to be able to target these two areas in discrete ways.

What are you working on now?As associate director for research and academic affairs, I work with other researchers and facilitate their research. Though it’s one step away from doing the research myself, it broadens research for me. Over the last year, I’ve tried to lay administrative groundwork and institute policies to free our researchers up so they can get their work done most effectively. Our clinical program at IDD is so strong—it’s been around for over 100 years—and our research teams are both independent and collaborative. It’s been rewarding to support their work. An example of what IDD is involved in is assistive technology, particularly in the area of communication. Charity Rowland, Ph.D., has an international research agenda and is involved in Design to Learn, an organization built by a group of IDD researchers and educators that develops assessment tools and teaching strategies for children and adults with severe disabilities. She collaborates with Melanie Fried-Oken, Ph.D., who has multiple projects, including ones with people who have locked-in syndrome, a condition in which most of the body is paralyzed but cognitive function is intact, helping them communicate.

As far as my personal research goes, I’m in the process of getting it started again and am bringing the work I did in Montana here to OHSU. Currently, I’m working in the community with people with disabilities who are living independently, as most of this population in Oregon does, either with family or on their own with needed supports. I’m trying to understand their food systems, the complexity of them. Once this is mapped out, we introduce some interventions or supports to help them manage this food system. When I was at the University of Montana, I created a product, Choice Food Routines for Independent Living, designed to help people with disabilities and/or their caregivers organize their food systems to set them up for healthy nutrition and sustainable food practices. I’m hoping to adapt this tool for Oregon and include it in a larger plan for all people with disabilities who receive services from the state.

This work is done with participatory methods. We have a number of partner groups that can serve in leadership roles: Parents who want their children to be independent and healthy, self-advocates who are living independently successfully, the support workers. Our partners include the Oregon Home Care Commission that trains personal support people in the state, and the Oregon Council on Developmental Disabilities and the Oregon Self-Advocacy Coalition. Oregon’s Parent Training and Information Center, FACT, the organizing group for families of children with disabilities in Oregon, is also involved. The drivers on some of these projects have been M.P.H. students from OSU, and as our new School of Public Health builds up, we’ll have even more students getting involved. My faculty appointment is with the School of Public Health. The interim dean, Elena Andresen, Ph.D., is a disability researcher who came from IDD, so I’m excited about the possible expansion of our programs through that school and the opportunity to support the new SPH with our active researchers’ participation there.

Our next step is to connect with service providers, brokerages, and the state to bring these interventions to the community. We’re trying to do more outreach and with the OHSU community and state to connect disability to the rest of the campus and community. We’re working with OCTRI to ensure people with disabilities are included in clinical trials and community work. NIH has made this a priority, so the IDD hopes to take the lead role in ensuring the inclusion of disability among the vulnerable populations targeted.

What do you like to do when you’re not at work?I like outdoor sports and do quite a bit of hiking and cycling. I’m also involved in the arts and just started back up with ballet, taking a class once a week. I’ve also noticed that people like to come to Portland so I’ve been hosting a lot and doing touristy things with out of town guests. It’s a great way to get to know the city! I have two active teenagers so they and their exciting lives soak up all the rest of my time when I am not in the CDRC building!